Aerosol delivery systems and methods

ABSTRACT

Methods and systems for aerosol delivery of agents to a patient are described herein. The present system can be used to administer various types of agents, such as a vaccine or other types of pharmaceutical substances. Certain embodiments of the present system utilize an actuator coupled to a disposable aerosolizing element that aerosolizes an agent for delivery to a patient when acted upon by the actuator. The aerosolizing element prevents the agent from contacting the actuator and other non-disposable components of the system so that little or no cleaning or maintenance is required. The present system also can include an aerosolization rate monitor that monitors the rate at which an agent is being aerosolized and provides feedback to the user to ensure that the proper dose is being administered.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.10/587,814, filed Jul. 28, 2006, which is a U.S. national stageapplication of PCT/US2005/011086, filed Apr. 1, 2005, which claims thebenefit of U.S. Provisional Application No. 60/559,318, filed Apr. 2,2004, all of which applications are incorporated herein by reference.

GOVERNMENT INTERESTS

This invention was made by the Centers for Disease Control andPrevention, an agency of the United States Government. Therefore, theUnited States Government may have certain rights in this invention.

FIELD

The present disclosure relates generally to the delivery of agents, andmore particularly, to systems and methods for delivery of agents usingaerosol devices.

BACKGROUND

Needles and syringes have posed a variety of problems for patients andmedical personnel who administer agents to the patients, includinginjection safety, needle stick injury, disposal problems, transmissionof blood borne diseases, and needle shortages during mass vaccinationcampaigns. The replacement of needles and syringes as the primarydelivery vehicle for agents has the potential for tremendous costsavings, increased safety and reduction of biomedical wastes.

Aerosol delivery of agents avoids many of the foregoing drawbacks ofinjection. Much of the equipment used for aerosol delivery is cumbersomeand has not been widely employed for many treatment methods. Nebulizersare commonly used in hospitals for aerosol delivery of agents in thetreatment of respiratory diseases. In practice, a nebulizer usescompressed gases to convert a solution of the agent into fine droplets.The droplets are administered to the patient through an air stream thatthe patient breathes inwardly through a mouthpiece or mask. As thepatient breathes, the agent is delivered to the patient's lungs andabsorbed therein.

Typically, nebulizers rely upon an external compressed gas source toconvert a solution of the agent into fine droplets. As a result of theneed for an external source of compressed gas, nebulizers tend to bebulky and difficult to move. Further, the effectiveness of a nebulizerdepends upon proper inhalation by the patient, which can be difficult tomonitor and to teach to the patient.

Currently used jet nebulizers function in the same general way. Liquidis drawn up to an air nozzle by capillary forces and/or the Bernoullieffect. At the nozzle, a high-speed air jet shatters the liquid intodroplets. Droplets blast against an impactor to break them up furtherinto smaller droplets. Like most atomization processes, this dropletgeneration process results in a size distribution. To obtain the desiredsmall aerosol droplets, baffles capture large droplets (which cannotfollow the airflow path well), leaving the fine aerosol in the outputstream of the nebulizer. The larger droplets recycle to the liquidreservoir of the nebulizer.

This nebulization process is inherently inefficient. Measurements showthat typical nebulizers only convert a few percent of the aspiratedliquid to fine aerosol droplets. Thus, liquid will normally be recycledwell in excess of twenty times before it reaches the desired size and isexhausted from the nebulizer. The inefficiency of the jet nebulizerposes problems to its use for aerosol vaccination. High velocity isneeded in the air jet to provide the energy required to break the liquidinto sufficiently small droplets, necessitating relatively high airsupply pressures in flow rates. Compressing air to provide this supplyrequires significant power, either human or electric.

Fluid recycling in the nebulizer in the small amount of vaccine requiredfor each dose results in the inability to operate on a dose-by-dosebasis. Many doses need to be present in the nebulizer in order fordroplet coalescence on the baffles in other surfaces to return liquid tothe reservoir. In addition, the repeated mechanical stress ofatomization on the vaccination particles in the liquid risks diminishingthe viability of the vaccine.

Another drawback of conventional nebulizers is that the components thatcome in contact with the agent being dispensed must be thoroughlycleaned after each session of use to prevent the growth of bacteria orother contaminants. Such cleaning and maintenance requirements pose amodest challenge in modern medical settings, but can prove to beextremely difficult to achieve with untrained personnel or inunderdeveloped regions of the world. Hence, conventional nebulizers areimpractical for use in mass vaccination campaigns, especially inunderdeveloped countries.

Existing vibrating mesh nebulizers have similar drawbacks. Vibratingmesh devices typically operate by ejecting droplets through tinyorifices of a thin plate (the “mesh”) that is vibrated ultrasonically byan actuator. Existing vibrating mesh devices place the agent to beaerosolized in direct contact not only with the mesh, but also with theactuator. In such devices, the mesh, actuator surfaces, and the fluidpathway in the device are intended for long-term single-patient use andmust be cleaned after each use. Cleaning of these devices under fieldconditions and their use in multi-patient settings, such as in massvaccination campaigns impose substantial difficulties and costs.

Monitoring or verifying the dose of aerosol delivered to a patient alsoposes a concern in the administration of aerosols (e.g., aerosolvaccination), especially when young children are involved. Unlikeinjection, where the delivery of a dose can be clearly observed, thedelivery of an aerosolized agent via a nebulizer is more difficult tomonitor.

Thus, a need exists for effective systems and methods for administeringan agent in an aerosol form, without a needle, and in more accuratedosages. Further, a need exists for delivery systems that are easier touse and maintain and reduce the likelihood of contamination, especiallyfor use in mass vaccination campaigns.

SUMMARY

The present disclosure concerns methods and systems, including devices,for delivery of agents that do not require use of needles to gain entryinto a biological system. More particularly, the present disclosureconcerns methods and systems for aerosolizing, or nebulizing, agents forpatient delivery. For example, such systems and methods can be used fordelivering agents such as pharmaceuticals, chemotherapeutics, immuneagents, and vaccines.

The present disclosure describes methods and systems for administeringone or more agents to multiple patients (either human or non-human) insingle dosage applications or to an individual patient for multipleadministrations. For example, many patients can be immunized with aninhaled vaccine composition using the present disclosure without theneed for needles or substantial cleaning or maintenance. In otherapplications, the composition may be administered to one individual.

An embodiment of the present disclosure comprises a portable aerosoldelivery device that includes a housing shaped to be held in a user'shand. The housing houses a disposable aerosolization element and anactuator that is operable to apply a moving force to the aerosolizationelement for aerosolizing an agent. The aerosolization element caninclude an integral reservoir in which there is stored a predeterminedvolume of agent. Alternatively, the aerosolization element can bedirectly coupled to a vial or container in which the agent is stored.For example, the aerosolization element can include a piercing prong orneedle that is inserted into a puncturable closure (e.g., a rubber cap)of a vial to allow agent stored in the vial to flow into theaerosolization element. The amount of agent stored in the aerosolizingelement and/or the vial can be sufficient for administering a singledose or multiple doses of the agent.

The aerosolization element defines an internal chamber that receivesagent from the reservoir and/or a vial coupled to the aerosolizationelement. One side of the chamber is partially bounded by an orificesurface defining a plurality of orifices. The opposite side of thechamber is partially bounded by a movable element that is coupled to theactuator. Vibratory oscillations of the actuator cause the movableelement to move alternately toward and away from the orifice surface. Asthe movable element moves closer to the orifice surface, the pressure inthe chamber increases and causes the agent to be expelled through theorifices in the form of aerosol droplets. As the movable element movesaway from the orifice surface, additional agent is drawn into thechamber to be aerosolized in the next cycle. When the aerosolizationelement (or the vial connected to the aerosolization element) is empty,the aerosolization element can be removed for disposal and replaced withanother aerosolization element.

Agent can be fed into the chamber of the aerosolization element eitherthrough gravity or capillary action. In the case of gravity feed, theagent is stored in the reservoir and/or a vial positioned above thechamber so that agent can flow into the chamber under the force ofgravity. In the case of capillary feed, the agent is stored in thereservoir and/or a vial positioned below the chamber and is drawnupwardly into the chamber by capillary action of the agent.

Advantageously, the aerosolization element prevents the agent fromcontacting the actuator and other non-disposable components of thedevice so that little or no cleaning or flushing of the device isrequired after each session. Consequently, unlike conventionalnebulizers, the device of the present disclosure is suitable for use inhigh-workload applications, such as mass immunization campaigns inunderdeveloped nations. Use of the aerosol delivery device also avoidsmany of the drawbacks of administering agents via injection, includingthe need for skilled personnel, the risk of blood-borne diseases, highcost, patient aversion to injection, and the need to safely dispose ofused needles and syringes.

In particular embodiments, the aerosol delivery device also includes anaerosolization rate monitor that monitors the rate at which the agent isbeing aerosolized. The aerosolization monitor includes a light source,such as a laser diode, for projecting a light beam across an aerosolplume emanating from the aerosolization element. A light detector, suchas a photodiode, detects the obscuration of the light beam, whichcorresponds to the concentration of aerosol droplets in the aerosolplume. The device can include a visual display, such as a digitalreadout, that displays the aerosolization rate to ensure that the properdosage is being administered. The device also can include an indicatorlight and/or an audible alarm for warning the user when theaerosolization rate is outside an acceptable range.

The aerosol delivery device includes a patient interface that deliversthe aerosolized agent to the mouth and/or nose of a patient. Oneembodiment of the patient interface includes an angled extension portioncoupled to the housing of the device and a disposable face mask that isshaped to cover the mouth and nose of the patient. In oneimplementation, the mask is made of a porous material that allowsexpiratory and inspiratory air to pass through the mask, but trapsexpired aerosol and particles (e.g., cough or sneeze particles). Inanother implementation, the mask is made of a non-porous material andthe extension portion is formed with one or more openings allowinginspiratory air to be drawn into the extension portion.

Another embodiment of the patient interface includes a one-way valvethat is operable to permit aerosolized agent to flow to the patient andrestrict flow in the opposite direction. The one-way valve can be, forexample, a flapper-type valve or “duckbill” type valve. The valveprotects the aerosolization element and other re-usable componentsagainst contamination caused by expired particles. In addition, theentire patient interface is disposable to further protect againstpatient-to-patient contamination.

The foregoing and other objects, features, and advantages of theinvention will become more apparent from the following detaileddescription, which proceeds with reference to the accompanying figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B are side views, shown partially in section, of anaerosol delivery device, according to one embodiment.

FIG. 2 is a side view of an aerosol delivery device, according toanother embodiment.

FIGS. 3A and 3B are side views, shown partially in section, of anaerosol delivery device, according to yet another embodiment.

FIGS. 4A and 4B are front elevation and cross-sectional views,respectively, of a removable and disposable aerosolization element foran aerosol delivery device, according to one embodiment.

FIG. 5 is cross-sectional view of an embodiment of a capillary feedaerosolization element for an aerosol delivery device.

FIG. 6 is a front elevation view of another embodiment of anaerosolization element for an aerosol delivery device.

FIGS. 7A and 7B are front elevation and cross-sectional views,respectively, of another embodiment of an aerosolization element for anaerosol delivery device.

FIGS. 8A and 8B are front elevation and cross-sectional views,respectively, of another embodiment of an aerosolization element that isused to store and mix two liquid components.

FIG. 8C is a cross-sectional view similar to FIG. 8B, showing theaerosolization element after the liquid components are mixed together toform an agent to be aerosolized.

FIG. 9A is a cross-sectional view of another embodiment of anaerosolization element that contains a liquid component separated from adry component.

FIG. 9B is a cross-sectional view similar to FIG. 9A, showing theaerosolization element after the liquid component and dry component aremixed together to form an agent to be aerosolized.

FIG. 10A is a front elevation view of another embodiment of anaerosolization element for an aerosol delivery device.

FIG. 10B is a cross-sectional view taken along line 10B-10B of FIG. 10A.

FIG. 10C is a magnified cross-sectional view of a portion of theaerosolization element.

FIG. 11 is an enlarged cross-sectional view of a patient interface shownbeing used with the aerosol delivery device of FIGS. 1A and 1B.

FIG. 12 is an enlarged cross-sectional view of another embodiment of apatient interface shown being used with the aerosol delivery device ofFIGS. 1A and 1B.

FIG. 13 is an enlarged cross-sectional view of another embodiment of apatient interface shown being used with the aerosol delivery device ofFIGS. 1A and 1B.

FIG. 14 is an enlarged cross-sectional view of another embodiment of apatient interface shown being used with the aerosol delivery device ofFIGS. 1A and 1B.

FIG. 15 is an enlarged cross-sectional view of another embodiment of apatient interface shown being used with the aerosol delivery device ofFIGS. 1A and 1B.

FIG. 16 is an enlarged cross-sectional view of a patient interface,according to another embodiment, shown being used with the aerosoldelivery device of FIGS. 1A and 1B and having a plurality of internalbaffles in the flow path to the patient.

FIGS. 17A and 17B are enlarged cross-sectional views of a patientinterface, according to another embodiment, showing the operation of aone-way valve in the patient interface permitting flow from the aerosoldelivery device to a patient, but inhibiting flow in the oppositedirection.

FIGS. 18A and 18B are enlarged cross-sectional views of a patientinterface, according to another embodiment, showing the operation of aone-way, duckbill valve in the patient interface.

FIGS. 19A and 19B are enlarged cross-sectional views of a patientinterface having a one-way valve, according to another embodiment.

FIGS. 20A and 20B are enlarged cross-sectional views of a patientinterface having a one-way valve, according to another embodiment.

FIG. 21A is a side elevation view of a piezoelectric actuator for anaerosol delivery device and a heat sink coupled to the actuator.

FIG. 21B is an end view of the heat sink shown in FIG. 21A.

FIGS. 22A, 22B, and 22C are front elevation, cross-sectional, andexploded views of an aerosolization element, according to anotherembodiment.

FIG. 23 is a cross-sectional view of another embodiment of an aerosoldelivery device.

FIGS. 24A and 24B are front and side elevation views, respectively, ofcomponents of the aerosol delivery device shown in FIG. 23.

FIG. 24C is a cross-sectional view taken along line 24C-24C of FIG. 24A.

DETAILED DESCRIPTION

As used herein, the singular forms “a,” “an,” and “the” refer to one ormore than one, unless the context clearly dictates otherwise.

As used herein, the term “includes” means “comprises.”

Agents, as used herein, comprise agents that can be administered toliving organisms for an effect in the treated organism. Such agentsinclude live and killed organisms for vaccination, immunogens, immuneactivators or suppressors, chemotherapeutics, pharmaceuticals, nucleicacids, insulin, hormones, antibodies and fragments thereof, receptors,proteins, carbohydrates, fats, nutrients, anesthetics, narcotics, andpain relievers.

The present disclosure is directed to methods and systems, includingdevices, for aerosol delivery of agents to a patient. The present systemcan be used to administer various types of agents, such as vaccines andother pharmaceutical substances. Use of the present system for agentdelivery, such as for vaccination purposes, provides many benefits. Forexample, the present system replaces the use of needles and syringes,and reduces the costs of agent delivery. Additionally, the presentsystem allows for treatment of patients by less-trained staff, anothercost saving benefit, and also helps prevent the spread of blood bornediseases by reused needles.

Certain embodiments of the present system utilize an actuator coupled toa disposable aerosolizing element that aerosolizes an agent for deliveryto a patient when acted upon by the actuator. The aerosolizing elementprevents the agent from contacting the actuator and other non-disposablecomponents of the system so that little or no cleaning or maintenance isrequired. The system therefore is well suited for use by less-trainedpersonnel in high-workload applications, such as mass vaccinationcampaigns.

The present system also can include an aerosolization rate monitor thatmonitors the rate at which an agent is being aerosolized and providesfeedback to the user to ensure that the proper dose is beingadministered. For example, the system can include an indicator lightthat illuminates or flashes if the aerosolization rate is outside anacceptable range.

Exemplary methods of the present disclosure comprise delivery of agentssuch as vaccine compositions. The methods of the present disclosurecomprise delivery of vaccine compositions via aerosol administration.The present disclosure contemplates the use of any vaccine compositionthat can be delivered via aerosol administration. Particularly preferredvaccination compositions are those for measles, mumps and rubella. Suchcompositions may comprise measles vaccine, mumps vaccine, rubellavaccine and combinations and mixtures such as measles and mumps, rubellaand mumps, measles and rubella, and measles, mumps and rubella. Thevaccines further comprise pharmaceutical or formulation components suchas those known in the art, including, but not limited to, diluents,compounding agents, surfactants, and agents to maintain sterility.

FIGS. 1A and 1B depict an aerosol delivery device 10, according to oneembodiment. The aerosol delivery device 10, includes a body, or housing12 formed with a handle portion 14 shaped to be held in a user's hand.The housing 12 in the illustrated embodiment houses a removableaerosolizing element 16, an actuator 18, and an air manifold 36substantially surrounding the actuator 18. The illustrated aerosolizingelement 16 is directly coupled to a vial 22 containing an agent (e.g., avaccine) to be administered to a patient. As described in detail below,the aerosolizing element 16 receives the agent from the vial 22 andexpels aerosol droplets through orifices 110 (FIG. 4A) for delivery to apatient upon activation of the actuator 18.

The housing 12 is formed with a movable front portion 24 that is mountedfor sliding movement in the directions indicated by double-headed arrow25 between a closed position (as shown in FIG. 1A) and an open position(as shown in FIG. 1B) to allow access to the aerosolizing element 16.When the front portion 24 is in the closed position, the aerosolizingelement 16 is held firmly in place between the front portion and theactuator 18. A latch mechanism 26 and a latch button 28 can be providedto releasably retain the front portion 24 in the closed position.Depressing the latch button 28 removes the latch mechanism 26 fromengagement with the front portion 24 so that it can be moved to the openposition. The front portion 24 desirably is adapted to be completelyremovable from the housing 12 for ease of cleaning. While theillustrated front portion 24 is mounted for sliding movement relative tothe housing 12 as shown, any other detachable connection can be used tomount the front portion 24 to the housing (e.g., adhesives, snapfittings, etc.).

Coupled to the housing 12 is a patient interface 30 for delivering anaerosolized agent to a patient. The illustrated patient interface 30includes a generally cylindrical extension portion 32 connected to themovable portion 24 and a disposable face mask 34 mounted to the upperend of the extension portion 32. The mask 34 is mounted to the extensionportion 32 in a removable manner so that the mask can be easily removedand replaced with a new mask for another patient. The extension portion32 includes a first portion 32 a extending through the front portion 24of the housing 12 and a second portion 32 b that extends upwardly at anangle with respect to the first portion 32 a. The extension portion 32may be of a rigid or flexible design and desirably is constructed from alow cost material, such as rubber, cardboard, fiberboard or plastic.

Generally, contaminants (e.g., expired particles from the patient) aredifficult to re-aerosolize unless they directly contact the surface ofthe aerosolizing element 16 adjacent the orifices 110 (FIG. 4A). Theangled second portion 32 b eliminates a direct pathway from the patientback to the aerosolizing element so as to prevent expired particles(e.g., cough and sneeze particles) from directly contacting theaerosolizing element 16. Hence, this protects against patient-to-patientcontamination if the aerosolizing element 16 is used to administer dosesto multiple patients. The face mask 34 can be made from a porous ornon-porous material, as further described below. Other types ofnon-disposable or disposable patient interfaces, such as nasal prongs,oral mouthpieces, and holding chambers, also can be used with theaerosol delivery device 10.

The actuator 18 is operable to apply a moving force to the aerosolizingelement 16, thereby causing the aerosolizing element to expel aerosoldroplets of an agent. The actuator 18 can be any type of oscillator thatcan apply vibratory oscillations to the aerosolizing element 16. As bestshown in FIG. 4B, the illustrated actuator 18 is a piezoelectric-drivenactuator (also known as an ultrasonic horn) that includes first andsecond electrodes 48 a, 48 b, a piezoelectric element 50 disposedbetween the first and second electrodes, and a motion transmittingmember 52 secured to the first electrode 48 a. An end portion 53 of themotion transmitting member is coupled to the aerosolizing element 16.

An oscillating electric current applied to the electrodes 48 a, 48 binduces vibratory motion of the piezoelectric element 50, which in turninduces vibratory motion of the motion transmitting member 52 in thedirections indicated by double-headed arrow 55. The motion transmittingmember 52 transmits the vibratory motion to the aerosolizing element 16for aerosolizing an agent therein. In particular embodiments, theactuator 18 generates vibrations in the range of about 20 to 200 Hz.Other types of actuators, such as a solenoid or a linear electric motor(e.g., a voice coil, such as used in a loudspeaker), also can be used toinduce vibration of the aerosolizing element.

As discussed above, the actuator 18 is mounted within the air manifold36, which directs compressed gas (e.g., compressed air) to flow over theactuator 18 and carry away heat generated during operation. The manifold36 is formed with a flow channel 38 substantially surrounding theactuator 18 and an opening 42 that is connected to a compressed airconduit 44. The air conduit 44 receives compressed air from a compressedair source, such as the illustrated air pump 46. The manifold 36 is alsoformed with one or more apertures 40, which direct air in the flowchannel 38 to flow through the aerosolizing element 16 in the directionof arrows 41. Air flowing through the aerosolizing element 16 entrainsaerosol droplets expelled from the aerosolizing element and assists inthe delivery of the droplets to the patient.

In lieu of or in addition to the air manifold 36, a heat sink 124 (FIGS.21A and 21B) can be mounted to the actuator 18 to facilitate thedissipation of heat generated during operation. As shown in FIGS. 21Aand 21B, the heat sink 124 includes a plurality of angularly spacedradial fins 126 extending longitudinally from a base 128 mounted to andin thermal contact with the actuator 18. In particular embodiments, theair manifold 36 can be sized to accommodate the actuator 18 and the heatsink 124. In other embodiments, the actuator 18 and optionally the heatsink 124 can be mounted in the housing 12 without the air manifold 36.In the latter embodiments, air from the air pump 46 can be ducteddirectly to the aerosolizing element 16 to assist in the delivery ofaerosolized agent to the patient.

As shown in FIGS. 1A and 1B, the device 10 can include a wearable orbody mountable pack or case 54 that houses the air pump 46 (e.g., adiaphragm air pump), an air filter 56, and one or more batteries 58 forpowering the device. The pack 54 can be, for example, a waist pack(“fanny pack”) that can be worn around the waist of a user or a shoulderor back pack that can be worn over one or both shoulders of a user. Thepack 54 also can include a controller 66, a charging jack 62 forre-charging the batteries 58, and an on/off power switch 61. Thecharging jack 62 can be connected to an external power supply (notshown) in a conventional manner to recharge the batteries 58 or toprovide power to operate the device without use of the batteries. Thepack 54 can be coupled to the housing 12 via a flexible umbilical 60that contains the air conduit 44 and wiring connecting the controller 66to the actuator 18 and a trigger switch 64 on the housing. By housingthe pump 46, the batteries 58, and the controller 66 in the pack 54, theoverall weight of the housing 12 can be reduced for easier handling. Inan alternative embodiment, one or more of these components can be housedin the handle portion 14 or in another portion of the housing.

Although not shown in the illustrated embodiment, a compressed airreceiver or reservoir can be housed in the handle portion 14 or the pack54. The air reservoir can have an inlet that receives compressed airfrom the air pump 46 via a first conduit and an outlet that supplies acharge of compressed air to the air manifold 36 via another conduit. Inanother embodiment, the handle portion 14 can be equipped with a handpump operable to charge the air receiver, such as disclosed inco-pending U.S. application Ser. No. 10/471,620 (U.S. Patent ApplicationPublication No. US-2004-0134494), which is incorporated herein byreference. The device 10 also can be equipped with a hand-crank dynamooperable to recharge the batteries 58, such as disclosed in the '620application.

The aerosol delivery device 10 can be operated in a continuous orautomatic dose timing mode. A selector switch (not shown) can beprovided on the handle portion 14 or on the pack 54 for manually settingthe device to operate in either mode. In the continuous mode, a userdepresses the trigger switch 64 on the handle portion 14, which sends asignal to the controller 66. The controller 66 sends a signal to the airpump 46 and the actuator 18 to begin operation. The aerosolizing element16 converts an agent drawn from the vial 22 into droplets of a verysmall size (e.g., in a range of about 1 to 10 micometers, although thesize of the droplets can vary depending on the application). Afteradministering a dose, the user depresses the trigger switch 64 again toturn off the actuator and the air pump.

In the automatic dose timing mode, the user first sets a timer switch(e.g., a rotary switch) (not shown) operatively connected to thecontroller at a desired setting corresponding to a predeterminedaerosolization period (e.g., 15, 20, 30, or 60 seconds). In alternativeembodiments, the device 10 can include a keypad or another type of inputdevice to allow the user to set the desired time of application. Toinitiate administration of a dose, the user depresses the trigger switch64, which activates the pump 46 to supply air to the manifold 36. Aftera predetermined period of time (e.g., 0.5 seconds), the actuator 18 isactivated to aerosolize the agent in the aerosolizing element 16. At theend of the aerosolization period, the actuator 18 is automaticallyturned off, after which the aerosolization element can be purged withcompressed air from the pump 46 for a predetermined period of time(e.g., 5 seconds) or until the switch 64 is depressed.

FIG. 2 shows another embodiment of the aerosol delivery device 10 thatis similar to the embodiment shown in FIGS. 1A and 1B, except that itincludes a hinged front portion 68 that is coupled to the housing 12 bya pivot pin 69. The front portion 68 is pivotable about the pin 69 (inthe directions indicated by double-headed arrow 70) between an openposition for removing or replacing the aerosolizing element 16 (as shownin FIG. 2) and a closed position in which the aerosolizing element 16 isheld firmly in place between the front portion 68 and the adjacentsurface of the housing 12. The housing 12 may be provided with a latch71 that engages a corresponding surface of the front portion 68 toreleasably retain the front portion 68 in the closed position. A latchbutton 72 on the latch 71 extends upwardly through the top of thehousing 12. Depressing the latch button 72 releases the latch 71 fromengagement with the front portion 68 so that it can be moved to the openposition shown in FIG. 2. Various other latch or lock mechanisms can beimplemented to releasably retain the front portion 68 in the closedposition.

FIGS. 3A and 3B show another embodiment of the aerosol delivery device10 that is similar in most respects to the embodiment shown in FIGS. 1Aand 1B. The embodiment of FIGS. 3A and 3B includes a housing 74 formedwith an upper opening 75 (FIG. 3B) that is sized to receive theaerosolizing element 16. As shown in FIG. 3A, when inserted into theopening 75, the aerosolizing element 16 is supported in an uprightposition by the top wall of the housing 74. The actuator 18 in thisconfiguration is coupled to a movable lever 76 that is operable to movethe actuator 18 between a first, operating position in which theactuator engages the aerosolizing element 16 (FIG. 3A) and secondposition in which the actuator is spaced from the aerosolizing element(FIG. 3B). The lower end of the lever 76 is pivotally mounted inside thehousing 74 at a pivot pin 77 to permit pivoting of the lever in thedirections indicated by double headed arrow 79. The upper end portion ofthe lever 76 extends through the top wall of the housing 74 formanipulation by a user. The actuator 18 is coupled to the lever 76 by apinned connection or equivalent mechanism such that the actuator 18 isdisplaced along a substantially straight path (in the directionsindicated by doubled-headed arrow 115) upon pivoting movement of thelever.

Prior to loading the aerosolizing element 16 into the housing, the lever76 is moved toward the rear of the housing to the position depicted inFIG. 3B. After insertion of the aerosolizing element, the lever is movedtoward the front of the housing to move the actuator 18 to the operatingposition depicted in FIG. 3A.

Turning now to FIGS. 4A and 4B, the aerosolizing element 16 will now bedescribed. The aerosolizing element 16 has a body 78 that includes afront portion 80, a rear portion 82, a chamber 84 cooperatively formedbetween the front portion 80 and the rear portion 82, and an integralreservoir 86 formed at the upper end portion of the aerosolizing elementand in fluid communication with the inlet of the chamber 84. A piercingprong, or needle, 88 extends upwardly from a vial mount 90 situated ontop of the reservoir 86. The prong 88 has a pointed upper end that isused to puncture a puncturable septum 92 incorporated or connected tothe opening of the vial 22. The septum 92 can be made of an elastomericmaterial (e.g., rubber) or any of various other suitable materials. Theprong 88 also functions to hold the vial 22 in an inverted position ontop of the vial mount 90. While the illustrated prong 88 is a smallcylindrical tube, other shaped tubes, including square, triangle, orrectangle, also can be used.

The prong 88 is formed with a first flow passageway 94 extending betweenthe upper end of the prong and the reservoir 86 to allow agent in thevial 22 to flow into the reservoir. A second flow passageway 96 in theprong 88 extends between the upper end of the prong and an air inlet, oropening, 98 formed in the vial mount 90. The opening 98 can be fittedwith a porous (air permeable) plug 100 (FIG. 4B). The second flowpassageway 96 allows atmospheric air to be drawn into the vial 22 toreplace agent that is extracted from the vial. The reservoir 86 also canbe provided with an air outlet, or opening, 102 (FIG. 4A) fitted with aporous plug (not shown) to allow for venting of air in the reservoir.The porous plugs in openings 98 and 102 are made of a material that ispermeable to air but inhibits leakage of the agent due to surfacetension.

The front portion 80 of the aerosolizing element 16 defines an orificesurface 104 that is formed with a plurality of orifices 110. The rearportion 82 defines a movable element 106 opposite the orifices 110 thatis coupled to the end portion 53 of the actuator 18. The movable element106 is movable or deformable to increase pressure in the chamber 84 inresponse to the force applied by the actuator 18. In the illustratedembodiment, for example, the movable element 106 comprises a flexiblediaphragm that alternately flexes inwardly and outwardly in response tomovement of the actuator. In operation, rapid motion of the actuator 18pushes the diaphragm inwardly and toward the orifices 110, increasingpressure in the chamber 84 and expelling agent outwardly through theorifices 110 to form aerosol droplets 108. Movement of the actuator 18in the opposite direction causes the diaphragm to flex outwardly andaway from the orifices, thereby decreasing the pressure in the chamber84 and drawing agent into the region of the chamber behind the orificesfor the next cycle. In alternative embodiments, the movable portion neednot be flexible or deformable but is otherwise configured to move towardand away from the front portion 80 in response to movement of theactuator 18.

As shown in FIG. 4A, the aerosolizing element 16 can be formed with oneor more air flow apertures, or openings, 112 extending through aperipheral portion of the element adjacent the orifice surface 104. Theopenings 112 are in fluid communication with the apertures 40 of the airmanifold 36 (FIG. 1B) at the rear surface of the element 16 so that airfrom the apertures 40 can flow through the openings 112 and entraindroplets 108 expelled by the orifices 110 for delivery to the patient.

The orifices 110 typically are about 5 micrometers in diameter, althoughthe size of the orifices can vary depending on the desired size of thedroplets 108. The front and rear portions 80, 82 can be made from any ofvarious suitable materials, such as plastic, using conventionalmanufacturing techniques (e.g., molding). The orifices 110 can be formeddirectly in the front portion 80 using conventional micro-machiningtechniques, such as laser drilling, electroforming, or chemical etching.As depicted in FIG. 4B, the rear portion 82 can be of a unitaryconstruction having a substantially constant thickness. In otherembodiments, the rear portion can have a relatively thinner sectionopposite the orifices 110 that defines the movable element 106. Inanother embodiment (e.g., the aerosolizing element 800 shown in FIGS.22A-22C, which is described below), the movable element can be aseparate element bounding the chamber opposite the orifices. In thelatter embodiment, the rear portion 82 can be formed with an opening toreceive the actuator 18 for coupling to the movable element.

Preferably, the aerosolizing element 16 is disposable. If the device isused where disposal costs are not prohibitive (e.g., in a modernhospital), the aerosolizing element (and the mask 34) can be disposed ofeach time a dose is administered to a patient. However, if the device isused in a high workload application, such as a mass vaccinationcampaign, disposal costs may be a concern. In such cases, theaerosolizing element can be used to administer doses to multiplepatients, but typically would be disposed of after a session ofadministering multiple doses to prevent the growth of bacteria or othercontaminants. Notably, the aerosolizing element 16 inhibits contact ofthe agent with the actuator 18 and other re-useable components of thedevice 10. Consequently, substantially less time is required forcleaning and maintenance of the device compared to conventionalnebulizers.

FIG. 5 shows an aerosolizing element 120, according to anotherembodiment, that can be used in any of the aerosol delivery devicesdescribed herein. The aerosolizing element 120 is similar to theaerosolizing element 16, except that agent is drawn upwardly to the areaof the chamber 84 behind the orifices 110 by capillary action. Theaerosolizing element 120 can be provided with a piercing prong 88 fordrawing agent upwardly from a vial 22 (not shown in FIG. 5).Alternatively, rather than drawing agent from a vial, the aerosolizingelement 120 can include an integral reservoir sized to receive apredetermined quantity of an agent sufficient for supplying a singledose or multiple doses.

The thickness of the chamber 84 (the distance measured between theopposed internal surfaces of the front and rear portions 80, 82) isselected to maintain an adequate flow of agent via capillary actionwithout inducing a pressure loss that exceeds the capillary head. Asshown, the aerosolizing element 120 can include one or more spaced apartdimples, or projections, 122 disposed in the chamber 84. The projections122 maintain a minimum spacing in the chamber 84 between the movableportion 106 and the front portion 80 of the element so as to maintainadequate capillary head without undue pressure loss.

FIG. 6 shows an aerosolizing element 130, according to anotherembodiment, that can be used in any of the aerosol delivery devicesdescribed herein. The aerosolizing element 130 has a body 132 thatincludes a first portion 134 and a second, deformable portion 136 thatserves as a reservoir for an agent to be aerosolized. The first portion134 has a construction that is similar to the aerosolizing element 16 inthat it includes an internal chamber (not shown) for receiving an agentto be aerosolized, an orifice area 136 defining a plurality of orifices138, and a movable portion (not shown) bounding the chamber opposite theorifices 138 for forcing agent through the orifices 138. The deformableportion 136 of the aerosolizing element 130 is made of a flexible,resilient material, such as rubber or another suitable elastomer. Apiercing prong 140 extends from the deformable portion 136 for insertioninto a vial 22. The piercing prong 140 is formed with an opening 144 toreceive agent from the vial. The deformable portion 136 functions in amanner similar to the squeeze bulb on a conventional eyedropper. Priorto inserting the prong 140 into a vial, the user squeezes the deformableportion 136. After insertion, finger pressure is removed from thedeformable portion 136, allowing it to return to its normal shape andthereby drawing agent from the vial via the prong 140. The agent in thedeformable portion 136 can be fed into the chamber of the first portion134 via gravity or capillary action, as described above in connectionwith the embodiments shown in FIGS. 4A, 4B, and 5.

FIGS. 7A and 7B show an aerosolizing element 150, according to anotherembodiment, that can be used in any of the aerosol delivery devicesdescribed herein. The aerosolizing element 150 has a body 152 thatincludes a front portion 154, a rear portion 156, a chamber 158cooperatively formed between the front portion 154 and the rear portion156, and an enlarged reservoir 160 formed at the upper end portion ofthe element and in fluid communication with the inlet of the chamber158. The reservoir 160 can be sized to hold a predetermined volume ofagent sufficient to deliver a single dose or multiple doses. Thereservoir 160 desirably is provided with a venting port 166 to exposethe interior of the reservoir to atmosphere when agent is drawn from thereservoir into the chamber 158. Although not shown in FIGS. 7A and 7B, aremovable piercing prong can be inserted into the venting port 166 forsupplying agent to the reservoir 160 from a vial 22. Additionally, thereservoir 60 can be filled via port 166 using a needle and syringe orequivalent device. The agent can be fed from the reservoir 160 into thechamber 158 via gravity or capillary action.

The front portion 154 is formed with an opening 162 (FIG. 7B) in whichthere is fitted an orifice plate 164 having multiple orifices forexpelling droplets of agent. In one implementation, the aerosolizingelement 150 is filled with a predetermined volume of agent and sealed bya pharmaceutical manufacturer or pharmacy. In this regard, a removablesealing tape 168 can be placed over the orifice plate 164 to preventleakage of agent and the ingress of foreign matter and other desiredmaterial into element prior to use. Likewise, a removable sealing tape170, a removable tab or other closure can be used to close the ventingport 166. The sealing tapes 168 and 170 are then removed by the userprior to administering the agent.

FIGS. 8A-8C show an aerosolizing element 180, according to yet anotherembodiment, that can be used in any of the aerosol delivery devicesdescribed herein. The aerosolizing element 180 differs from thepreviously described embodiments in that it can be used to store and mixtwo different liquid components. As shown, the aerosolizing element 180has a body 182 that includes a front portion 184, a rear portion 186, achamber 188 cooperatively formed between the front portion 184 and therear portion 186, a first reservoir 190 in fluid communication with theinlet of the chamber 188, and a second reservoir 192 defined at theupper end portion of the aerosolizing element. An orifice plate 164 isdisposed in an opening formed in the front portion 184.

As shown in FIG. 8B, the chamber 188 and the first reservoir 190 arefilled with a first liquid and the second reservoir 192 is filled with asecond liquid. A plug, or separation element, 194 is disposed in theaerosolizing element 180 between the first and second reservoirs to keepthe liquids separated from each other prior to use. The second reservoir192 has an open top that is fitted with a plug 196. A removable, annularring 198 is disposed around the plug 196 and seated against the open endof the second reservoir 192. The plug 196 is formed with an annularflange portion 197 that overlaps the ring 198. The ring 198 preventsinadvertent or premature mixing of the first and second liquids byresisting movement of the plug 196 into the second reservoir 192.

To reconstitute the first and second liquids at the time of use, theuser removes the ring 198 and pushes down on the plug 196 to pressurizethe second reservoir 192. Due to the incompressibility of the liquid,the liquid forces the plug 194 into the wider area of the firstreservoir 190, thereby allowing the liquid in the second reservoir tomix with the liquid in the first reservoir (as shown in FIG. 8C). Inuse, the agent can be fed from the reservoir 190 into the chamber 188via gravity or capillary action.

FIGS. 9A and 9B show an aerosolizing element 200, according to yetanother embodiment, that can be used in any of the aerosol deliverydevices described herein. The aerosolizing element 200 differs from thepreviously described embodiments in that it can be used to store and mixa liquid component and a dry component (e.g., a solid or powderedcomponent). As shown, the aerosolizing element 200 has a body 202 thatincludes a front portion 204, a rear portion 206, a chamber 208cooperatively formed between the front portion 204 and the rear portion206, a first reservoir 210 in fluid communication with the inlet of thechamber 208, and a second reservoir 212 defined at the upper end portionof the aerosolizing element. An orifice plate 164 is disposed in anopening formed in the front portion 204.

As shown in FIG. 9A, the chamber 208 and the first reservoir 210 arefilled with a liquid (e.g., a diluent for a dry component) and thesecond reservoir 212 is filled with a powder (e.g., lyophilate) oranother type of dry component. A plug 214 is disposed in theaerosolizing element 200 between the first and second reservoirs to keepthe dry component separated from the liquid component prior to use. Thesecond reservoir 212 has an open top that is fitted with a plug 216. Arigid push rod 218 (e.g., a glass rod) extends from the plug 216 andcontacts the plug 214 (FIG. 9A). The body 202 can be formed with aventing port 220 between the first and second reservoirs 210 and 212adjacent the plug 214. As shown in FIG. 9A, the plug 214 covers the port220 to prevent leakage prior to use.

To reconstitute the liquid and dry components at the time of use, theuser removes the ring 198 and pushes down on the plug 216. Movement ofthe plug 216 and the push rod 218 forces the plug 214 into the widerarea of the first reservoir 210, thereby allowing the dry component inthe second reservoir to mix with the liquid in the first reservoir andform an agent for administering to a patient (as shown in FIG. 9B).Displacement of the plug 214 also exposes the first reservoir 210 toatmospheric pressure via the venting port 220 to facilitate the flow ofagent into the chamber 208. In use, the agent can be fed from thereservoir 210 into the chamber 208 via gravity or capillary action.

FIGS. 10A-10C show an aerosolizing element 250, according to anotherembodiment, that can be used in any of the aerosol delivery devicesdescribed herein. The aerosolizing element 250 has a body 252 thatincludes a front portion 254, a rear portion 256, a chamber 258cooperatively formed between the front portion 254 and the rear portion256, and an integral reservoir 260 formed at the upper end portion ofthe aerosolizing element and in fluid communication with the inlet ofthe chamber 258. The reservoir 260 desirably is provided with a ventingport 266 to expose the interior of the reservoir to atmosphere pressurewhen agent is drawn from the reservoir into the chamber 258. In use, theagent can be fed from the reservoir 260 into the chamber 258 via gravityor capillary action.

The front portion 254 is formed with an opening in which there is fittedan orifice plate 164 for expelling droplets of agent. The body 252further includes peripheral portions 268, 270 on opposite sides of thechamber 258 (FIG. 10A). Formed in the peripheral portions 268, 270 arerespective air flow passageways 272 (FIGS. 10B and 10C). As best shownin FIG. 10C, each passageway 272 extends from an inlet 274 formed in therear portion 256 to one or more outlets 276 formed in the front portion254 at locations offset from the inlet 274. When the aerosolizingelement 250 is placed in the housing of an aerosol delivery device(e.g., the device 10 shown in FIGS. 1A and 1B), the inlets 274 arepositioned to receive compressed air from the air manifold 36. Air flowsinto the inlets 274, through the passageways 272 and exits the outlets276 (as indicated by arrows 278) to entrain droplets expelled by theorifice plate 164. Because the outlets 276 are offset from the inlet274, there is less likelihood that expired particles from the patientcan travel through the passageways and contact the actuator 18 or otherreusable portions of the system.

FIGS. 22A-22C show an aerosolizing element 800, according to anotherembodiment, that can be used in any of the aerosol delivery devicesdescribed herein. The aerosolizing element 800 has a body 802 thatincludes a front portion 804, a rear portion 806, and a reservoir 810formed at the upper end portion of the aerosolizing element. Thereservoir 810 desirably is provided with a venting port 812.

Disposed between the front and rear portions 804, 806 is an orificeplate 814 (e.g., an electroformed mesh plate) and a flexible spacerelement 816. A chamber 808 for receiving agent from the reservoir 810 isdefined between the orifice plate 814 and the spacer element 816. Theorifice plate 814 is formed with a plurality of orifices 818 that arealigned with an opening 820 in the front portion 804. The spacer element816 is formed with a plurality of projections 824 that maintain aminimum spacing in the chamber 808 between the orifice plate 814 and thespacer element 816. Although not required, the orifice plate 814 and thespacer element 816 can be held together by a piece of adhesive tape 826placed over the orifice plate and secured to the lower end portion ofthe spacer element for ease of assembly. The tape 826 is formed with anopening 828 aligned with the opening 820 in the front portion 804. Therear portion 806 is formed with an opening 836 that is sized to receivethe front end portion 53 of the actuator 18 (FIG. 4B). A piece ofdouble-sided tape 840 can be used to secure the end portion 53 of theactuator 18 to the spacer element 816. A suitable sealant (e.g.,silicone) can be used to secure the tape 826 to the inside surface 832of the front portion 804 and to secure the spacer element 816 to theinside surface 834 of the rear portion 806.

In particular embodiments, the orifice plate 814 comprises a thin metalfoil (e.g., nickel, aluminum, gold, or another suitable metal) having athickness of about 0.05 mm. Other suitable materials, such as ceramicsor composite materials, also can be used to form the orifice plate 814.The orifices 818 can be formed using conventional micro-machiningtechniques, such as laser drilling, electroforming, and chemicaletching. The spacer element 816 comprises a thin flexible plastic havinga thickness of about 0.1 mm. The projections 824 on the spacer element818 have a height of about 0.1 mm. Of course, these specific dimensions(as well as other dimensions provided in the present specification) andmaterials are given to illustrate the invention and not to limit it. Thedimensions and materials provided herein can be modified as needed indifferent applications or situations.

The spacer element 816 serves as a flexible diaphragm for expellingagent through the orifice plate 814. In use, the end portion 53 of theactuator 53 extends through the opening 836 and bears against the spacerelement 816. Vibration of the actuator 18 is transmitted to the spacerelement 816, causing it to flex toward and away from the orifice plate814, alternately forcing agent in the chamber 808 through the orifices818 and drawing agent into the chamber 808 from the reservoir 810.

FIG. 11 shows an extension portion 300 of a patient interface that canbe used with the aerosol delivery device 10 (or other delivery devices),according to another embodiment. The extension portion 300 is similar tothe extension portion 32 shown in FIGS. 1A and 1B, except that theextension portion 300 includes one or more openings, or vents, 302proximate the housing 12. A disposable mask 34 (not shown in FIG. 11)can be coupled to the end of the extension portion 300 in the mannershown in FIGS. 1A and 1B. The openings 302 allow inspiratory air to bedrawn into the extension portion 300, as indicated by arrows 304, so asto allow the patient to breathe normally during the administration of anagent. As outside air enters the extension portion, the air entrainsaerosol droplets expelled by the aerosolizing element 16 to assist inthe delivery of droplets to the patient.

FIG. 12 shows a patient interface 350 that can be used with the aerosoldelivery device 10 (or other delivery devices), according to anotherembodiment. The patient interface 350 includes an extension portion 352extending from the housing 12 and a disposable mask 354 coupled to theend of the extension portion 352. The extension portion 352 includes aone-way valve 356 that is operable to allow inspiratory air to flow intothe extension portion and inhibit flow in the opposite direction to thesurrounding environment. The illustrated valve 356 includes an opening358 formed in the extension portion 352 and a flexible sealing member360 secured at one end to the inside surface of the extension portion.The sealing member 360 can be made from a flexible and/or elastomericmaterial, such as rubber or any of various other suitable elastomers. Inits normal, at rest position, the sealing member 360 covers the opening358. During inhalation, the sealing member 360 opens to allow outsideair to be drawn into the extension portion through the opening 358 (asindicated by arrow 370) to assist in the delivery of aerosol droplets tothe patient. During exhalation, the sealing member 360 covers theopening 358 to prevent aerosolized agent in the extension portion frombeing released to the surrounding environment.

The mask 354 in this embodiment is made of a non-porous material (amaterial that does not allow passage of air) and includes a one-wayvalve 362 to allow for the release of expiratory flow. The valve 362houses a flexible sealing member 364 that covers openings 366 in themask in its normal, at rest position to prevent outside air from flowinginto the mask. During exhalation, the sealing member 364 opens to allowexpiratory air to flow through openings 366 and openings 368 to theenvironment.

FIG. 13 shows a patient interface 400 that can be used with the aerosoldelivery device 10 (or other delivery devices), according to anotherembodiment. The patient interface 400 includes an extension portion 402extending from the housing 12 and a disposable mask 404 coupled to theend of the extension portion 402. The mask 404 in this embodiment ismade of a porous material that allows for the passage of air. The mask404 can be manufactured from, for example, nonwoven polypropylene, suchas used in conventional surgical or dust masks, or other suitablematerials. Expiratory and inspiratory air can flow through the mask 404(as indicated by double-headed arrows 406), but traps expiredparticulates (e.g., cough and sneeze particles) and aerosolized agent inthe mask from being released to the environment. The extension portion402 can include a one-way valve 356 (FIG. 12) to permit outside air bedrawn into the flow path and assist in the delivery of aerosol dropletsexpelled by the aerosolizing element 16.

FIG. 14 shows a patient interface 450 that can be used with the aerosoldelivery device 10 (or other delivery devices), according to anotherembodiment. The patient interface 450 includes an extension portion 454extending from the housing 12, a disposable mask 456 coupled to the endof the extension portion 454, and an air distribution plenum 458co-axially disposed around the horizontal portion of the extensionportion 454. A compressed air conduit 460 is connected to an air inlet462 of the plenum 458 to deliver compressed air from the pump 46 (FIGS.1A and 1B) (or another source of compressed air) to the plenum 458. Theextension portion 454 is formed with one or more openings 464 inside ofthe plenum 458. In use, compressed air from the conduit 460 flows intothe plenum 458, though openings 464 and into the extension portion 454(in the direction of arrows 466). The air flow from the plenum furtherassists in the delivery of the aerosol droplets to the patient andreduces aerosol deposition on the internal surfaces of the extensionportion by directing the aerosol droplets away from these surfaces.

FIG. 15 shows a patient interface 500 that can be used with the aerosoldelivery device 10 (or other delivery devices), according to anotherembodiment. The patient interface 500 includes a first portion 502extending from the housing 12 and a second, enlarged portion 504 sizedto cover the nose and mouth of a patient. The patient interface 500 ismade of a porous material to allow for the passage of expiratory andinspiratory air along the entire length of the interface. In theparticular embodiments, the entire patient interface 500 is intended tobe disposed of after each use to protect against patient-to-patientcontamination.

FIG. 16 shows a patient interface 550 that can be used with the aerosoldelivery device 10 (or other delivery devices), according to anotherembodiment. The patient interface 550 includes a first portion 552extending from the housing 12 and a second, enlarged portion 554 sizedto cover the nose and mouth of a patient. A plurality of baffles 556 arespaced along the length of the first portion 552 and extend into theflow path of aerosol droplets expelled from the aerosolizing element 16.The baffles 556 shield the aerosolizing element 16 and other re-usablecomponents from expired particles (e.g., cough or sneeze particles) toprotect against patient-to-patient contamination. In the illustratedembodiment, the first portion 552 is made of a non-porous material andthe second portion 554 is made of a porous material. The first andsecond portions 552, 554 can be secured to each other using suitabletechniques or mechanisms, such as adhesives or fasteners. Alternatively,the entire patient interface 550 can be made from single piece of porousmaterial, similar to the patient interface 500 of FIG. 15, or from twoseparately formed pieces of porous material that are joined together toform the patient interface. The patient interface 550, like the patientinterface 500, preferably is disposable.

FIG. 17A and 17B shows a patient interface 600, according to anotherembodiment, that includes a first portion 602 extending from the housing12 and a second, enlarged portion 604 sized to cover the nose and mouthof a patient. The second portion 604 is made of a porous material whilethe first portion 602 may be made of a porous or non-porous material.The patient interface 600 is similar to the patient interface 550 ofFIG. 16, except that the patient interface 600 includes a one-way valve606 disposed in the first portion 602. The valve 606 is a flapper-typevalve having a flexible sealing member 608 secured at one end to theinside surface of the first portion 602 and a non-movable valve seat 610secured at one end to the inside surface of the first portion 602opposite the sealing member 608.

In its normal, at rest position, the sealing member 608 contacts orpartially overlaps the valve seat 610 to close the flow path from theaerosolizing element 16 to the patient (FIG. 17B). During inhalation,the sealing member 608 opens to allow aerosol droplets and air to flowto the patient (FIG. 17A). During exhalation, the valve closes (FIG.17B) to protect the aerosolizing element 16 and other re-useablecomponents against contamination from expired particles. In anotherembodiment, the patient interface 600 can include both the valve 606 andbaffles 566 (FIG. 16) to further protect against contamination. Thepatient interface 600, like the patient interface 500, preferably isdisposable.

FIGS. 18A and 18B shows a patient interface 650, according to anotherembodiment, that includes a first portion 652 extending from the housing12 and a second, enlarged portion 654 sized to cover the nose and mouthof a patient. The second portion 654 is made of a porous material whilethe first portion 652 may be made of a porous or non-porous material.The patient interface 650 is similar to the patient interface 600 ofFIGS. 17A and 17B, except that the patient interface 650 includes aone-way, “duckbill” type valve 656 disposed in the first portion 652.The valve 656 includes first and second flexible sealing members 658,each of which is connected to the inside surface of the first portion652. The sealing members 658 extend toward and contact each at theirfree ends so as to close the flow path from the aerosolizing element 16to the patient when the valve is in its normal, at rest position (FIG.18B). The sealing members 658 may be made of any of various suitableelastomeric materials. During inhalation, the sealing member 658 open toallow aerosol droplets and air to flow to the patient (FIG. 18A). Duringexhalation, the valve closes (FIG. 18B) to protect the aerosolizingelement 16 and other re-useable components against contamination fromexpired particles. The patient interface 650, like the patient interface500, preferably is disposable.

FIGS. 19A and 19B shows a patient interface 700, according to anotherembodiment, that includes a first portion 702 extending from the housing12 and a second, enlarged portion 704 sized to cover the nose and mouthof a patient. The second portion 704 is made of a porous material whilethe first portion 702 may be made of a porous or non-porous material.The patient interface 700 includes a one-way flapper-type valve 706 thatincludes a flexible sealing member 708 secured at one end to the insidesurface of the first portion 702. A generally rigid seating member 710is secured to the first portion 702 opposite the flexible sealing member708. The seating member 710 is angled away from the housing 12 andextends to a location at or above the longitudinal center of the patientinterface 700 so as to shield the aerosolizing element 16 from expiredparticles. The valve 706 operates in similar manner to the valve 606shown in FIGS. 17A and 17B to allow flow from the aerosolizing element16 to the patient and restrict flow in the opposite direction duringexhalation. The patient interface 700, like the patient interface 500,preferably is disposable.

FIGS. 20A and 20B shows a patient interface 750, according to anotherembodiment, that includes a first portion 752 extending from the housing12 and a second, enlarged portion 754 sized to cover the nose and mouthof a patient. The second portion 754 is made of a porous material whilethe first portion 752 may be made of a porous or non-porous material.The patient interface 750 includes a one-way valve 756 that includes agenerally rigid seating member 758 secured to the first portion 752. Ahinge assembly includes a support plate 762 secured to the first portionopposite the seating member 758 and a sealing member 760 pivotallyconnected to the support plate 762 for pivoting movement in thedirections indicated by double-headed arrow 764. In its normal at restposition, the sealing member 760 rests against the seating member 758(FIG. 20B) to close the valve. During inhalation, the sealing member 760pivots upwardly and away from the seating member 758 to allow aerosoldroplets and air to flow to the patient (FIG. 20A). During exhalation,the sealing member 760 returns to the closed position to restrict flowin the opposite direction (FIG. 20B).

Although the patient interfaces shown in FIGS. 11-20 are shown beingused in an aerosol delivery device having an actuator 18 and anaerosolizing element 16, this is not a requirement. Accordingly, thepatient interfaces can be implemented in other types of aerosol deliverysystems, such as jet nebulizer systems and pneumatic aerosol deliverysystems.

FIGS. 23 and 24A-24C show an aerosol delivery device 900, according toanother embodiment. The aerosol delivery device 900 includes a body, orhousing, 902 formed with a handle portion 904 shaped to be held in auser's hand. The housing 902 houses a removable aerosolizing element906, an actuator 18, and an air manifold 908 substantially surroundingthe actuator 18. The aerosolizing element 906 has a construction that issimilar to the construction of the aerosolizing element 800 shown inFIGS. 22A-22C. Thus, components in FIGS. 23 and 24A-24C that are similarto components in FIGS. 22A-22C are given the same reference numerals andare not described further. As shown in FIG. 23, the aerosolizing device906 further includes a piercing prong 970 extending from a venting port972 into a vial 22.

The handle portion 904 houses an air pump 910 that is fluidly coupled tothe air manifold 908 via an air conduit 912. A first indicator light 962on the housing 902 provides a visual indication of whether an agent isbeing aerosolized. A second indicator light 964 provides a visualindication of whether the aerosolization rate is outside apredetermined, acceptable range. The indicator lights 962, 964 can be,for example, LEDs or lamps.

A front portion 914 of the housing 902 is mounted for sliding movementtoward and away from the aerosolizing element 906, as indicated bydouble-headed arrow 916. In its closed, operating position (as shown inFIG. 23), the front portion 914 holds the aerosolizing element 906firmly in place against the actuator 18. The front portion 914 can bemoved to an open position spaced from the housing 902 to access theaerosolizing element 906.

A latch mechanism 918 for releasably retaining the front portion 914 inthe closed position comprises a button 920 extending through thehousing, a lever 922 connected to the housing by a pivot pin 928, and alatch pin 924 extending upwardly into a corresponding latch opening inthe front portion 914. One end the lever 922 is coupled to the latch pin924 and the opposite end of the lever bears against the button 920. Atorsion spring 926 disposed around the pivot pin 928 biases the lever922 in the counterclockwise direction in FIG. 23 to retain the latch pin924 in the latch opening in the front portion 914. Depressing the button920 moves in the lever 922 in the clockwise direction, which in turnremoves the latch pin 924 from the latch opening so that the frontportion 914 can be moved to the open position. The front portion 914desirably is completely removable from the housing 902 for ease ofcleaning.

The front portion 914 defines an air flow plenum 930 in fluidcommunication with the manifold 908 and a co-axially extending innerconduit 932 that receives aerosolized agent from the aerosolizingelement 906. The inner conduit 932 is formed with one or more openings934 in fluid communication with the air flow plenum 930. Coupled to thefront portion 914 is a patient interface 936 that includes an upwardlyangled extension portion 938 and a disposable face mask 940. Theextension portion 938 desirably is connected to the forward portion 914in a removable manner for ease of cleaning or for disposal.

In use, air from the air pump 910 flows into the manifold 908 via theconduit 912 to cool the actuator 18. A portion of the airflow is ductedinto the internal conduit 932 via openings 98 in the aerosolizingelement 906 (FIG. 24C) to assist in carrying aerosol droplets to thepatient. Another portion of the airflow in the manifold 908 is ductedinto the air flow plenum 930 and then into the inner conduit 932 viaopenings 934, as indicated by arrows 942. The airflow from the plenum930 assists in preventing deposition of aerosol droplets on the innerconduit 932 by directing the flow of aerosol droplets away from theinner surface.

The aerosol delivery device 900 also includes an aerosolization ratemonitor that is operable to monitor the rate at which an agent is beingaerosolized by the aerosolizing element 906 by detecting the obscurationof a light beam passing through an aerosol plume emanating from theaerosolization element 906. Referring also to FIGS. 24A-24C, theaerosolization rate monitor includes a light source 944 (e.g., a diodelaser or a light emitting diode (LED)) and a light detector, or sensor,946 (e.g., a photodiode), both of which are coupled to the rear surfaceof the manifold 908. First and second passageways 948 and 950,respectively, extend between the front and rear surfaces of the manifold908. The aerosolization element 906 includes first and second reflectors952 and 954, respectively, positioned on opposite sides of an orificeplate 814. Each reflector 952, 954 has a reflective surface 958positioned at approximately a 45 degree angle with respect to the firstand second passageways 948, 950 in the manifold 908.

The light source 944 projects a light beam through the first passageway948, the aerosolization element 906, and onto the reflective surface 958of the first reflector 952. The first reflector 952 reflects the lightbeam across the aerosol plume emanating from the aerosolization element906 and onto the reflective surface 958 of the second reflector 954. Thesecond reflector 954 reflects the light beam back through theaerosolization element 906 and the second passageway 950 toward thelight detector 946. The aerosolization element 906 desirably is made ofa transparent material (e.g., clear plastic) to transmit the incidentand reflected light beam. Alternatively, the aerosolization element 906can be made of a non-transparent material having openings aligned withthe first and second passageways 948, 950 to allow the incident andreflected light beam to pass through the aerosolization element. Thereflective surfaces 958 can be formed by applying reflective paint or alayer of reflective material (e.g., reflective tape) on the reflectors952, 954.

As the aerosol plume passes through the reflected light beam (as bestshown in FIG. 24C), the light detector 946 detects the obscuration ofthe light beam, which corresponds to the concentration of aerosoldroplets in the aerosol plume. The light detector 946 relays a signal toa controller 960 (FIG. 23), which determines the aerosolization rate. Ifthe aersolization rate is outside of the acceptable range, the indicatorlight 964 illuminates or begins flashing to provide a visual indicationof this condition. The system 900 also can include a digital readout 966(FIG. 23) mounted at a convenient location on the housing 902 to providea digital readout of the aerosolization rate. Other indicating devices,such as an audible alarm, also can be used to provide the userinformation regarding the operating status of the system.

The system 900 also can be equipped with a counting device that countsor records the number of doses administered and the amount of each dose.In one implementation, for example, the controller 960 can have memoryfor recording dose information (e.g., number and amount of each dose)and other information regarding the operation of the system. Informationrecorded in the memory can be displayed on the digital readout 966. Thedevice 900 also can include a removable memory device (e.g., a flashmemory card) for storing such operating information. Additionally, acommunication port (not shown) can be provided to allow operatinginformation of the device 900 to be communicated to a general purposecomputer (e.g., a laptop) via a cable or a wireless connection.

In view of the many possible embodiments to which the principles of thedisclosed invention may be applied, it should be recognized that theillustrated embodiments are only preferred examples of the invention andshould not be taken as limiting the scope of the invention. Rather, thescope of the invention is defined by the following claims. We thereforeclaim as our invention all that comes within the scope and spirit ofthese claims.

1. An aerosolizing device, comprising: a housing sized and shaped to be held in a hand of a user; a disposable aerosolizing element coupled to the housing and capable of expelling aerosolized agent, the aerosolizing element comprising a body defining a chamber, agent releasing orifices defined in the body and in communication with the chamber, and a movable portion positioned opposite the agent releasing orifices; and an actuator disposed in the housing and positioned to exert vibratory oscillations on the movable portion of the disposable aerosolizing element to aerosolize agent in from the chamber of the aerosolizing element, the actuator comprising a piezoelectric element and a motion transmitting member that is operable to transmit vibratory motion of the piezoelectric element to the movable portion such that the moveable portion moves toward the orifices to cause agent in the chamber to be expelled through the orifices; wherein the aerosolizing element is configured to prevent agent from contacting the motion transmitting member and the piezoelectric element and to prevent expired particles or contaminants from a patient from contacting the motion transmitting member and the piezoelectric element; wherein the disposable aerosolizing element is removable from the housing for installation and disposal.
 2. The device of claim 1, further comprising a patient interface coupled to the aerosolizing element and shaped to deliver aerosolized agent expelled from the disposable aerosolizing element to a patient.
 3. The device of claim 1, wherein the motion transmitting member has an end surface that is adhesively secured to the movable portion of the aerosolizing element.
 4. The device of claim 3, wherein the motion transmitting member is adhesively secured to the movable portion with double-sided adhesive tape having one side adhesively secured to the end surface of the motion transmitting member and another side adhesively secured to the movable portion.
 5. The aerosolizing element of claim 1, wherein the movable portion is deformable, and the movable portion deforms when the vibratory motion is transmitted to the movable portion so as to increase pressure in the chamber, thereby expelling agent from the chamber through the orifices.
 6. The aerosolizing element of claim 5, wherein the movable portion comprises a flexible diaphragm.
 7. The aerosolizing element of claim 6, wherein the body comprises a rear wall, the rear wall comprising an opening adjacent the flexible diaphragm, and the motion transmitting member extends through the opening in the rear wall.
 8. The device of claim 1, further comprising a compressed air source configured to supply compressed air to the device to assist in delivery of aerosolized agent to the patient.
 9. The device of claim 8, wherein some of the air conveyed by the compressed air source is directed to cool the oscillator.
 10. The device of claim 2, further comprising air inlet holes positioned to allow entry of atmospheric air into the device to assist in delivery of aerosolized agent through the patient interface.
 11. The device of claim 1, wherein the disposable aerosolizing element has an internal chamber at least partially defined by a flexible portion that can be manually squeezed by a user to create a negative pressure within the chamber to assist in filling the chamber with agent.
 12. The device of claim 1, further comprising: a power source for the device comprising one or more batteries.
 13. The device of claim 12, further comprising an air pump and an air conduit fluidly connecting the air pump to the housing, the air pump being operable to supply compressed air to the housing to assist in delivery of aerosolized agent to the patient.
 14. The device of claim 2, wherein the patient interface comprises a disposable mask shaped to fit around the mouth and nose of the patient.
 15. The device of claim 14, wherein the mask comprises a material that is porous to air.
 16. The device of claim 2, wherein the patient interface comprises a one-way valve that is operable to permit flow from the disposable aerosolizing element to the patient through the patient interface, and to inhibit flow in the reverse direction through the patient interface.
 17. The device of claim 16, wherein the one-way valve comprises a duckbill valve.
 18. The device of claim 2, wherein the patient interface comprises one or more baffles that shield the disposable aerosolizing element from expired particles.
 19. The device of claim 2, wherein the patient interface is a nasal prong.
 20. The device of claim 1, further comprising a counting device that is operable to record the number of doses that are administered by the device.
 21. The device of claim 1, further comprising an aerosolization rate monitor that is operable to detect the rate at which agent is aerosolized by the aerosolizing element.
 22. The device of claim 21, wherein the aerosolization rate monitor comprises a light source operable to project a light beam that extends through aerosol droplets being expelled by the aerosolizing element and a light detector operable to detect the obscuration of the light beam caused by the aerosol droplets.
 23. The device of claim 22, wherein the aerosolization rate monitor comprises a controller and a visual indicator, wherein the controller receives the signal from the light detector and determines an aerosolization rate based on the signal, and the visual indicator provides a visual indication regarding the aerosolization rate.
 24. The device of claim 22, wherein the aerosolizing element comprises first and second reflective surfaces, the first reflective surface being positioned to reflect the light beam from the light source to extend in a first direction through the aerosol droplets, the second reflective surface being positioned to reflect the light beam extending through the aerosol droplets to extend in a second direction toward the light detector.
 25. The device of claim 2, wherein a fluid passageway from a source of agent to the patient interface is substantially contained within the aerosolizing element.
 26. The device of claim 25, wherein the source of agent is contained within the aerosolizing element.
 27. The device of claim 25, wherein the aerosolizing element is shaped for direct connection to the source of agent.
 28. The device of claim 1, wherein the aerosolizing element is pre-filled with a volume of agent for providing at least one dose to the patient.
 29. The device of claim 28, wherein the volume of agent is sufficient for delivery of multiple single doses.
 30. The device of claim 1, further comprising a vial containing agent for direct coupling to the aerosolizing element.
 31. The device of claim 1, further comprising projections disposed in the chamber of the aerosolizing element, the projections configured to maintain a minimum spacing in the chamber between the orifices and the movable portion.
 32. The device of claim 31, wherein the projections are disposed on the movable portion.
 33. The device of claim 1, wherein a pathway for the aerosolized agent from the aerosolizing element to the patient is entirely outside of the housing.
 34. An aerosolizing device, comprising: a housing sized and shaped to be held in a hand of a user; a disposable aerosolizing element disposed in the housing and capable of expelling aerosolized agent, the aerosolizing element comprising a body defining a chamber, agent releasing orifices defined in the body and in communication with the chamber, and a movable portion positioned opposite the agent releasing orifices; and an actuator disposed in the housing and positioned to exert vibratory oscillations on the movable portion of the disposable aerosolizing element to cause the moveable portion to move toward and away from the orifices, the motion of the moveable portion causing agent in the chamber to be expelled through the orifices; wherein the aerosolizing element is configured to prevent agent from contacting the actuator and to prevent expired particles from a patient from contacting the actuator; wherein a pathway for the aerosolized agent from the aerosolizing element to the patient is entirely outside of the housing.
 35. The device of claim 34, wherein the disposable aerosolizing element is removable from the housing and replaceable with a new aerosolizing element for use of the device with a different patient without cleaning the actuator. 